Aula 2 - Neoplasia: Genetics and Environment Flashcards
1
Q
Definition:
Neoplasia
A
Abnormal and uncontrolled growth of cells, typically as a consequence of alterations of the cellular function, which can be benign or malign.
2
Q
True or False:
Neoplasia results in solid tumors.
A
False.
Neoplasia might result in the formation of tumors, but not all neoplasia result in solid tumors, such as hematological cancers.
3
Q
Distinguish:
Benign vs. Malign neoplasia
A
- Benign neoplasia: the cells grow slower and are contained in the origin tissue or organ, as they are unable ti metastasize;
- Malign neoplasia: the cells grow quickly and are able to metastasize, invading other tissues and/or organs besides their origin.
4
Q
Truth or False:
Neoplasia and Cancer are synonyms.
A
False.
Neoplasia is an abnormal and uncontrolled growth of cells, which can be benign or malign. A malign neoplasia can also be called Cancer.
5
Q
Definition:
Tumor
A
“Mass-effect” or space-occupying lesion resultant from an increase of a certain tissue or region. In other words, it is a solid mass made resultant from increased cell growth.
6
Q
True or False:
Neoplasia may not always lead to solid tumors, but tumors are always a result of neoplasia.
A
False.
It is true that neoplasia does not always lead to the formation of solid tumors (for example, in the case of hematological cancers). But tumors can also be a consequence of inflammatory reactions or fluid accumulation, which means they aren’t only a consequence of neoplasia.
7
Q
List:
Neoplasia risk factors
A
- Environmental factors
- Inherit genetics
- Age
- Gender
- Ethnicity and race
- Viruses, parasites and bacteria
- Complications from previous pathologies and/or commorbities
8
Q
Examples:
Environmental risk factors of Neoplasia
A
- Raditation exposure (such as ionizing radiation, which can damage DNA);
- Chemical exposure (such as arsenic, asbestos, etc.);
- Tobacco and exhaustion gases;
- Alcohol (since it is decomposed into acetaldeyde in the body, which damages DNA).
9
Q
True or False:
Cancer can be passed through generations.
A
False.
Cancer itself cannot be passed between generations, but genetic alterations associated with a higher predisposition to develop cancer can be passed down.
10
Q
Question:
Why is age a risk factor of Neoplasia?
A
With aging:
* The immune system becomes weaker and less efficient;
* There is an increase of genomic instability;
* There is a cumulative effect of life-long exposure to environmental factors, viral infections, etc.
11
Q
Question:
Why is gender a risk factor of Neoplasia?
A
- Societal behaviours, habits and lifestyle;
- Hormonal differences;
- Anatomical differences;
- Occupational jobs.
12
Q
Question:
Why are ethnicity and race risk factors of Neoplasia?
A
- Inherent genetic factors;
- Different lifestyle habits;
- Exposure to different environmental factors;
- Disparities in access to healthcare.
13
Q
Question:
Why are virsuses, parasites and bacteria risk factors of Neoplasia?
A
- They weaken the immune system, leaving the body more susceptible to cancer-causing infections;
- They may interfere with normal signaling pathways involved in cell growth and proliferation check points.
14
Q
Examples:
3 viruses associated with cancer
A
Any 3 of the following:
* Epstein-Barr Virus
* Hepatitis B Virus
* Hepatitis C Virus
* Human Immunodeficiency Virus (HIV)
* Human Papillomaviruses (HPVs)
* Human T-Cell Leukemia/Lymphoma Virus Type 1
* Kaposi Sarcoma-Associated Herpesvirus
* Merkel Cell Polyomavirus
15
Q
Question:
Why is obesity considered a commorbity and a risk factor of Neoplasia?
A
Obesity is associated with a higher risk of developing some types of cancer, since it is associated with an increased production of insulin (in response to inflammatory processes) and estrogen (produced by fat tisssue), which trigger cell growth.
16
Q
Question:
Why is type 2 Diabetes considered a commorbity and a risk factor of Neoplasia?
A
Type 2 Diabetes causes insulin resistance, which means the body can’t use insulin properly to keep the blood sugar at normal levels, so they become higher than normal. Insulin resistance does not mean insulin deficiency - quite the opposite, it is associated with excess insulin. Since insulin is known to promote cell division, excess insulin may make the organism more susceptible to develop neoplasia.
17
Q
Question:
What are the 3 classification systems of Neoplasia?
A
- Prognostic-based classification;
- Histogenic-based classification;
- Tumor-Nodes-Metastasis (TNM)-based classification.
18
Q
Question:
How can a neoplasia be classified according to prognostic-based classification?
A
- Benign;
- Malign;
- Borderline behaviour.
19
Q
Question:
Characterize malign neoplasms in terms of cellular morphism, nucleus, mitosis and polarity.
A
- Cellular morphism: pleomorphism (variable in size and shape) and anaplasia (loss of function and structure);
- Nucleus: big and hyperchromic (dark color), with a prominent nucleolus;
- Mitosis: abundant and atypical;
- Polarity: absent.
20
Q
True or False:
Ki-67 can be used as a proliferation marker.
A
True.
When Ki-67 is a nuclear protein that is released during cellular division. Therefore, when there is a high concentration of Ki-67, it means many cells are dividing quickly, so the cancer is more likely to grow and spread.
21
Q
Complete the sentence:
The histogenic-based classification classifies neoplasms based on the type of ____________ where they are located.
A
tissue
22
Q
Question:
How can a neoplasia be classified according to histogenic-based classification?
A
Based on the type of tissue:
- Epithelial;
- Mesenchymal or connective tissue;
- Muscle;
- Neural tissue;
- Hematologic;
- Endothelial tissue.
23
Q
Question:
What are the type of tissues associated with carcinoma and sarcoma?
A
Epithelial tissue and connective tissue, respectively.
24
Q
Complete the sentence:
Leukemia is a type of malign neoplasia that is located in ________ tissues.
A
hematological
25
# **Question:**
What is the Tumor-Nodes-Metastasis classification based on?
* Primary tumor size;
* Lymph node status (if they are swollen and/or lumpy and where they are located);
* Metastasis (by testing sentinel lymph nodes for cancer cells).
26
# **Question:**
What are the 3 phases of carcinogenesis?
1. **Initiation**: induction of DNA mutations;
2. **Promotion**: proliferation/replication of mutated cells;
3. **Progression**: acquisition of malignant properties, such as migration, invasion and metastasis.
27
# **Question:**
What is the role of cell cycle checkpoints?
They are surveillance mechanisms that monitor and control the normal cell cycle, to ensure the apropriate cell size and the replication and integrity of chromossomes.
28
# **Complete the sentence:**
At the cell cycle checkpoints, ________ are responsible of dictating the progression to the next phase of the cycle, while ________ may hold or interrupt the cell cycle progression.
| Words: cyclins, retinoblastoma protein, p53, p21
## Footnote
(NOTE: each space can have more than one word)
* first space: cyclins
* second space: retinoblastoma protein, p53, p21
29
# **True or False:**
The initiation phase of carcinogenesis begins with the lesions caused by carcinogenic agents.
**False.**
Carcinogenic agents may induce DNA mutations and damage cells, but these lesions can either be repaired or reproduced. The initiation phase of carcinogenesis begins **when the lesions can't be repaired**, not exactly when they are made.
30
# **Distinguish:**
Initiator vs. Promoter carcinogenic agent
* **Initiator** carcinogenic agent induces non-lethal mutations, causing irreversible changes to DNA;
* **Promoter** carcinogenic agent induces cell proliferation without affecting the DNA, such that its influence on cell growth is reversible.
## Footnote
(NOTE: some carcinogenic agents are both initiators and promoters)
31
# **True or False:**
Tumor supressor genes are mutations that are disadvantageous for tumor cells.
**False.**
Tumor supressor genes are mutated genes that confer advantages to tumor cells due to **loss of function**, typically as a result of frame-shift or deletion mutations.
32
# **Distinguish:**
Tumor supressor genes vs. Oncogenes
* **Tumor supressor genes** are mutated genes that confer advantages to tumor cells due to **loss of function**, typically as a result of frame-shift or deletion mutations;
* **Oncogenes** are mutated genes that confer advantages to tumor cells due to **gain of function**, typically as a result of amplification or overexpression of genes, as well as chromosomal translocations.
33
# **Question:**
What are the type of genes involved in carcinogenesis?
Tumor suppressor genes and oncogenes.
34
# **Question:**
In which 4 main cell mechanisms can mutated genes (tumor suppressor genes and oncogenes) interfere in?
1. Regulation of DNA repair;
2. Regulation of apoptosis (programmed cell death);
3. Growth factor signaling pathways;
4. Cell adhesion.
35
# **Question:**
Why is cell adhesion important?
* Cell-cell interaction/communication (e.g., symbiotic interactions);
* Cell-extracellular matrix interaction;
* Survival (including nutrition);
* Proliferation and differentiation;
* Tissue structure and integrity;
* Migration (including metastasis in cancer cells).
etc.
36
# **Question:**
What is the role of **cyclins** in the cell cycle?
Cyclins bind to cyclin-dependent kinases (CKD) in order to form complexes able to phosphorylate proteins from different checkpoints. Once phosphorylated, these proteins **allow the cell cycle to proceed to the next phase**.
37
# **True or False:**
Cyclin levels are overall stable throughout the cell cycle, contrarily to CKD proteins, such that the deregulation of genes involved in CKD production might affect the cell cycle progression.
## Footnote
(NOTE: CKD corresponds to cyclin-dependent kinases)
**False.**
While CKD levels are stable throughout the cell cycle, **cyclin levels vary**. Therefore, the lack of regulation (deregulation) of the genes involved in the production of cyclins might affect the progression of the cell cycle.
38
# **Question:**
What is the role of the **MYC oncogene**?
**Promotes the transcription of cyclin genes**, increasing the levels of cyclin and promoting the progression of the cell cycle. Therefore, it ultimately leads to an uncontrolled proliferation (cell growth and differentiation), while also inhibiting apoptosis.
39
# **Question:**
What is the role of **p53** in the cell cycle?
P53 is a transcription factor that is **activated by DNA damage, hypoxia or cell injury**. It works by activating p21, which in turn inhibits the cyclin complexes, thus stopping the cell cycle. If the damage is beyond repair, p53 can also **induce apoptosis**.
40
# **Question:**
Why is **p53 tumor suppressor** considered a tumor biomarker?
P53 tumor suppressor inhibits the activation of p53, which allows the cell cycle to progress despite DNA damage. It is considered a tumor biomarker because it is associated with multiple tumors.
41
# **True or False:**
Rb and p53 are both transcription factors that are activated by DNA damage, hypoxia and cell injury, capable of inducing apoptosis if the damage is beyond repair.
**Truth.**
42
# **Question:**
What is the role of the **Rb tumor suppressor**?
The Rb tumor suppressor inhibits the activation of Rb, allowing the cell cycle to progress despite DNA damage.
43
# **Question:**
What is the role of **retinoblastoma (Rb) protein** in the cell cycle?
Rb is a transcription factor that is activated by DNA damage, hypoxia and cell injury. It commands DNA repair mechanisms and induce apoptosis if damage is beyond repair.
44
# **Complete the sentence:**
When activated, Rb can bind with the transcription factors of the ________ family, forming complexes that inhibit the transcription of genes that allow cell cycle progression (such as cyclin).
E2F
45
# **Question:**
What are **BRCA**?
BRCA are a group of **DNA repair proteins** that resolve DNA crosslinks.
46
# **Question:**
What are the most common BRCA mutations and what type of cancers are they usually associated with?
The most common BRCA mutations, called **BRCA tumor suppressor**, are in the BRCA1 and BRCA2 genes, and they are often associated with breast and ovarian cancer.
47
# **Question:**
What is the role of the **BRCA tumor suppressor**?
BRCA tumor suppressor is related with mutations in BRCA1 or BRCA2 genes, which makes them lose their normal functions, leading to defective DNA repair and increasing the risk of accumulating mutations that evolve to cancer.
48
# **Complete the sentence:**
BCL-2 is a ________ protein, while BAX and BAK are ________ proteins.
anti-apoptotic, pro-apoptotic
49
# **True or False:**
BCL-2 is a pro-apoptotic protein.
**False.**
BCL-2 is an anti-apoptotic protein, whose overexpression due to BCL-2 oncogene may prevent apoptosis of cancer cells, allowing them to proliferate.
50
# **Question:**
What are the 2 most common **growth factor receptors** that are overexpressed or mutated in cancer?
* Epidermal growth factor receptors (EGFR);
* Epidermal growth factor receptor 2 (HER2).
51
# **Question:**
What are **growth factor receptors** (GFR)?
Growth factor receptors (GFR) are transmembrane proteins are proteins found on the surface of cells that bind to specific growth factors, which are molecules that signal the cell to proliferate (i.e., grow and divide).
52
# **Question:**
What is the **EGFR oncogene**?
The EGFR oncogene is a mutation that causes the **overexpression of the epidermal growth factor receptors (EGFR)**, allowing the survival and proliferation of cancer cells.
53
# **Question:**
What is the **Ras gene family**?
Familiy of genes that make proteins involved in cell signaling pathways/cascades that control cell growth and cell death (apoptosis).
54
# **Question:**
What is the **Ras oncogene**?
The Ras oncogene is a result of a mutation in the Ras gene family, leading to the dysregulation of major signaling cascades, thus resulting in sustained survival and proliferation of cancer cells.
55
# **Question:**
What types of cancer is **MYC oncogene** associated with?
* Burkitt lymphoma (a type of B-cell cancer);
* Small-cell lung cancer;
* Breast cancer;
* Neuroblastoma (malignant tumor in nerve cells).
56
# **Complete the sentence:**
MYC oncogene ________ (increases/decreases) the production of cyclins.
increases
57
# **Question:**
What types of cancer is **Rb tumor suppressor** associated with?
* Retinoblastoma (malignant tumor in retina);
* Small-cell lung cancer;
* Sarcoma (cancer in connective tissue).
58
# **Question:**
What types of cancer is **BCL-2 oncogene** associated with?
* Lymphomas;
* Leukemias;
* Lung cancer.
59
# **Question:**
What types of cancer is **EGFR oncogene** associated with?
* Lung cancer;
* Gliobastoma (malignant tumor in glial cells);
* Breast cancer.
etc.
60
# **Question:**
What types of cancer is **Ras oncogene** associated with?
* Pancreatic cancer;
* Lung cancer;
* Colon cancer;
* Leukemia.
61
# **Examples:**
Cell adhesion molecules
* Cadherins
* Integrins
* Selectins
62
# **Question:**
What type of cancer is **APC tumor suppressor** associated with?
Colon cancer
63
# **Question:**
What is the effect of the APC tumor suppressor gene?
The APC tumor suppressor gene has negative effects on APC proteins, making them promote migration, chromosomal instability and evasion of apoptosis, which allows cancer cells to migrate more easy and invade other tissues.
64
# **Distinguish:**
Neoadjuvant vs. Adjuvant treatment
* **Neoadjuvant treatment**: other therapies before surgery;
* **Adjuvant treatment**: surgery before other therapies.
65
# **Question:**
What are the 6 signs that a cancer cell is in its Progression phase?
1. Self-sufficient signs of growth;
2. Insensitivity to growth inhibitory signals;
3. Evasion to apoptosis;
4. Unlimited replicative potential;
5. Sustained angiogenesis;
6. Ability to invade and metastasize.
66
# **Definition:**
Angiogenesis
Formation of new blood vessels from pre-existing ones.
67
# **Question:**
What is the process that leads to tumor angiogenesis?
Tumors have a high metabolism, which means they require a lot of energy, nutrients and oxygen to support the rapid cell growth. In response to a lack of oxygen (hypoxia) and nutrients, cancer cells release angiogenic factors and promote the formation of new blood vessels surrounding the tumor - angiogenesis. Therefore, tumor angiogenesis result from the tumor's need to grow.
68
# **Question:**
What is the relation between angiogenesis and metastasis?
Angiogenesis is the formation of new blood vessels, typically as a result of a lack of oxygen and nutrients to meet the needs of a rapidly growing tumor (with a high metabolism). These new vessels are very close to the tumor cells, increasing the risk of these cells to enter the blood and migrate to other tissues, creating metastasis.
In short, angiogenesis may promote metastasis.
69
# **True or false:**
Tumor angiogenesis is promoted by chemotaxis.
**True.**
Tumor angiogenesis is promoted by nutrient and chemical concentrations (which in this case are lower that what is needed).
70
# **Complete the sentence:**
Dissemination of cancer cells can occur through ________ vessels and ________ vessels.
blood, lymphatic
71
# **Question:**
What are the 2 main factors that determine which type of vessel the cancer cells will intravasate?
* **Physical restrictions** (like proximity, fenestrations and flow mechanisms);
* **Active mechanisms for attracting cells** for specific types of vessels (like the presence of angiogenic factors).
72
# **Question:**
Describe the process of **dissemination through blood vessels**.
Tumor cells from the primary tumor:
1. Enter the blood vessels through fenestrations (**intravasation**);
2. Form an **embolus** (unattached mass that travels through the bloodstream);
3. **Adhere to vessels** membrane;
4. Escape the blood vessel through fenestrations (**extravasation**);
5. Start a **metastatic growth**.
73
# **Question:**
Is it possible to delay the process of dissemination through blood vessels? How?
Yes.
The dissemination of tumor cells through blood vessels is highly dependent on angiogenesis, which is mediated by angiogenic growth factors. So, by **counteracting** their effects using **anti-angiogenic growth factors**, it is possible to delay angiogenesis and thus the dissemination of tumor cells through blood vessels.
74
# **Question:**
Describe the process of **dissemination through lymphatic vessels**.
1. The primary tumor produces **lymphangiogenic factors**, which enter the **peritumoral lymphatic capillaries**;
2. The lymphangiogenic factors are transported up to the **sentinel lymph node** (SNL) and induce **SNL lymphangiogenesis** (formation of new lymphatic vessels) to drain the tumor;
3. These **tumor-draining vessels** have an enlarged size (with larger fenestrations, thus easier entrance) and increased lymph flow (facilitating the migration of tumor cells);
4. The lymphangiogenic factors **promote rearrangements and remodeling of smooth muscle cells** of the lymphatic vessels post-SNL;
5. The lymphangiogenic factors and metastatic cells from the lymph nodes can then pass through those vessels and reach **distal lymph nodes**;
6. There is the **promotion of secondary metastasis**.
75
# **Question:**
Each neoplasia might present different clinical manifestations, depending on which 3 factors?
* Neoplasia location;
* Neoplasia staging and degree of differentiation;
* Neoplasia ability to produce humoral factors.
76
# **Question:**
What the 3 main types of clinical manifestations of neoplasia?
* Mechanical injuries;
* Biological competition;
* Production of humoral factors.
77
# **List:**
5 types of mechanical injuries
1. Obstruction
2. Bleeding
3. Fistulation
4. Perforation
5. Compression of neighbouring structures
78
# **Question:**
What is **cachexia**?
Cachexia is a clinical manifestation of biological competition typically seen in patients in an advanced cancer stage. It consists of a complex syndrome that essentially leads to the ongoing muscle and fat loss due to increased lipolysis and proteolysis.
79
# **Question:**
Why is **anemia** a common clinical manisfestation of neoplasia?
Anemia is common in neoplasia due to:
* Hemolysis;
* Bleeding (constant loss of red blood cells and iron);
* Chronic disease;
* Chemotherapy;
* Medullar invasion (disrupting the production of red blood cells);
* Malnutrition (cancer patients usually feel sick and can't eat properly, leading to a poor intake of iron).
80
# **Distinguish:**
Signs vs. Symptoms
**Signs** can be seen by others and measured (e.g., fever), while **symptoms** are only perceived by the patient (e.g., pain).
81
# **Definition:**
Paraneoplastic syndromes
Set of signs and symptoms occuring in an oncologic situation, not directly related with the primary tumor or metastasis. They might appear in response to secondary changes in the body (e.g. in response to the elevation of a certain protein or hormone).
82
# **Definition:**
Hypercoagulability or thrombophilia
Increased tendency of blood to coagulate and form a thrombi.
83
# **True or False:**
Cancer can cause acquired hypercoagulability.
**True.**
84
# **Question:**
Why is the rate of cancer mortality increasing despite the increase in cancer research?
Due to the increase in the number of risk factors, besides the long time it takes to approve treatments (around 10 years).
85
# **True or False:**
Targeted therapy is a type of localized cancer treatment.
**False.**
Targeted therapy is a type of **systemic cancer treatment**, since it goes through the blood stream (systemically) and is able to reach the desired location.
86
# **Complete the sentence:**
Cancer treatments can be divided in ________ treatments, such as radiotherapy, and ________ treatments, such as targeted therapy.
localized, systemic
87
# **Questions:**
What are the 2 main types of localized cancer treatment?
* Sugery;
* Radiotherapy, which includes external irradiation and internal irradiation (brachytherapy).
88
# **Question:**
What are the 4 main types of systemic cancer treatment?
* Chemotherapy;
* Hormonal therapy;
* Targeted therapy;
* Immunotherapy.
89
# **True or False:**
Localized cancer treatment requires a more detailed and well defined plan, compared to systemic treatment.
**True.**
